Modification of the cysteine residues in IkappaBalpha kinase and NF-kappaB (p65) by xanthohumol leads to suppression of NF-kappaB-regulated gene products and potentiation of apoptosis in leukemia cells.

ABSTRACT: Xanthohumol (XN), a prenylated chalcone isolated from hop plant, exhibits anti-inflammatory, antiproliferative, and antiangiogenic properties through an undefined mechanism. Whether examined by intracellular esterase activity, phosphatidylserine externalization, DNA strand breaks, or caspase activation, we found that XN potentiated tumor necrosis factor-induced apoptosis in leukemia and myeloma cells. This enhancement of apoptosis correlated with down-regulation of nuclear factor-kappaB (NF-kappaB) survivin, bcl-xL, XIAP, cIAP1, cIAP2, cylin D1, and c-myc. XN down-regulated both constitutive and inducible NF-kappaB activation, inhibition of phosphorylation and degradation of IkappaBalpha, suppression of p65 nuclear translocation, and NF-kappaB-dependent reporter gene transcription. XN dire

SUBMITTER: Harikumar KB 

PROVIDER: S-EPMC2947354 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature